Scheduling Decisions 1107 Final

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FINAL DECISIONS amp REASONS FOR DECI SIONS BY DELEGATES OF THE

SECRETARY TO THE DEPARTMENT OF HEALTH AND AGEING

JULY 2011

Delegatersquos final decision on a scheduling matter considered as a delegate-only matterie was not referred for advice to an expert advisory committee meeting

Notice under subsection 42ZCZX of the Therapeutic Goods Regulations 1990(the Regulations)

A delegate of the Secretary to the Department of Health and Ageing hereby givesnotice of a delegatersquos final decision for amending the Poisons Standard (commonlyreferred to as the Standard for the Uniform Scheduling of Medicines and Poisons ndashSUSMP) under subsections 42ZCZX of the Regulations This notice also providesthe reasons for the decision and the date of effect of the decision

Matters not referred to an advisory committee

A delegate may decide not to refer a matter to an advisory committee and instead may

make a final decision on the matter Guidance for the delegate when deciding not torefer a matter to an advisory committee is set out in the Scheduling Policy Framework(SPF) accessible at wwwtgagovauindustryscheduling-spfhtm

Implementation

The amendments arising from this notice will be incorporated into the SUSMPthrough a special amendment (SUSMP No 1 Amendment 3) An electronic copy of SUSMP No 1 Amendment 3 will be available on the ComLaw website a link towhich can be found at wwwtgagovauindustryscheduling-poisons-standardhtm

The next SUSMP consolidation (SUSMP No 2) will also contain these amendments

and hardcopies of the consolidation will be available for purchase from August 2011from National Mailing and Marketing Pty Ltd telephone (02) 6269 1035 A hardcopyof SUSMP No 1 Amendment 3 will not be produced



Delegatesrsquo reasons for final decisions July 2011 i

TABLE OF CONTENTS

GL OSSARY II FINAL DECISIONS ON MATTERS NOT REFERRED TO AN ADVISORY COMMITTEE 1 1 MEDICINES 1

11 S YNTHETIC CANNABINOIDS 1



Delegatesrsquo reasons for final decisions July 2011 ii

GLOSSARY

ABBREVIATION NAME

AAN Australian Approved Name

AC Active Constituent

ACCC Australian Competition and Consumer Commission

ACCM Advisory Committee on Complementary Medicines (formerlyComplementary Medicine Evaluation Committee [CMEC])

ACNM Advisory Committee on Non-prescription Medicines (formerly

Medicines Evaluation Committee [MEC])

ACPM Advisory Committee on Prescription Medicines (formerlyAustralian Drug Evaluation Committee [ADEC])

ACSOM Advisory Committee on the Safety of Medicines (formerlyAdverse Drug Reactions Advisory Committee [ADRAC])

ADEC Australian Drug Evaluation Committee (now AdvisoryCommittee on Prescription Medicines [ACPM])

ADI Acceptable Daily Intake

ADRAC Adverse Drug Reactions Advisory Committee (now AdvisoryCommittee on the Safety of Medicines [ACSOM])

AHMAC Australian Health Ministers Advisory Council

APVMA Australian Pesticides and Veterinary Medicines Authority

AQIS Australian Quarantine and Inspection Service

ARfD Acute Reference Dose

ASCC Australian Safety and Compensation Council

ASMI Australian Self-Medication Industry

ARTG Australian Register of Therapeutic Goods



Delegatesrsquo reasons for final decisions July 2011 iii

CAS Chemical Abstract Service

CHC Complementary Healthcare Council of Australia

CMEC Complementary Medicine Evaluation Committee (now AdvisoryCommittee on Complementary Medicines [ACCM])

CMI Consumer Medicine Information

COAG Councils Of Australian Governments

CRC Child-Resistant Closure

CTFAA Cosmetic Toiletry amp Fragrance Association of Australia

ECRP Existing Chemicals Review Program

EPA Environment Protection Authority

ERMA Environmental Risk Management Authority (NZ)

FAISD First Aid Instructions and Safety Directions

FDA Food and Drug Administration (US)

FOI Freedom of Information Act 1982

FSANZ Food Standards Australia New Zealand

GHS Globally Harmonised System for Classification and Labelling of Chemicals

GIT Gastro-intestinal tract

GP General Practitioner

HCN Health Communication Network

HCP Health Care Provider

INN International Non-proprietary Name

ISO International Standards Organization



Delegatesrsquo reasons for final decisions July 2011 iv

LC50 The concentration of a substance that produces death in 50 of apopulation of experimental organisms Usually expressed as mgper litre (mgL) as a concentration in air

LD50 The concentration of a substance that produces death in 50 of apopulation of experimental organisms Usually expressed asmilligrams per kilogram (mgkg) of body weight

LOAEL Lowest Observed Adverse Effect Level

LOEL Lowest Observed Effect Level

MCC Medicines Classification Committee (NZ)

MEC Medicines Evaluation Committee (now Advisory Committee on

Non-prescription Medicines [ACNM])

MOH Ministry of Health (NZ)

NCCTG National Coordinating Committee of Therapeutic Goods

NDPSC National Drugs and Poisons Schedule Committee (now replacedby the Secretary of the Department of Health and Ageing [orSecretaryrsquos delegate] as scheduling decision-maker)

NHMRC National Health and Medical Research Council

NICNAS National Industrial Chemicals Notification amp Assessment Scheme

NOAEC No Observed Adverse Effect Concentration

NOAEL No Observed Adverse Effect Level

NOEL No Observable Effect Level

NOHSC National Occupational Health amp Safety Commission

OCM Office of Complementary Medicines

OCSEH Office of Chemical Safety and Environmental Health

ODA Office of Devices Authorisation

OMA Office of Medicines Authorisation (was Office of Prescriptionand Non-prescription Medicines)



Delegatesrsquo reasons for final decisions July 2011 v

OOS Out of Session

OTC Over-the-Counter

PACIA Plastics And Chemicals Industries Association

PAR Prescription Animal Remedy

PBAC Pharmaceutical Benefits Advisory Committee

PEC Priority Existing Chemical

PGA Pharmaceutical Guild of Australia

PHARM Pharmaceutical Health and Rational Use of Medicines

PI Product Information

PIC Poisons Information Centre

PSA Pharmaceutical Society of Australia

QCPP Quality Care Pharmacy Program

QUM Quality Use of Medicines

RFI Restricted Flow Insert

SCCNFP Scientific Committee on Cosmetic and Non-Food Products

SCCP Scientific Committee on Consumer Products

STANZHA States and Territories and New Zealand Health Authorities

SUSDP Standard for the Uniform Scheduling of Drugs and Poisons (nowthe Standard for the Uniform Scheduling of Medicines and

Poisons [SUSMP])

SUSMP Standard for the Uniform Scheduling of Medicines and Poisons

SVT First aid for the solvent prevails

TCM Traditional Chinese Medicine



Delegatesrsquo reasons for final decisions July 2011 vi

TGA Therapeutic Goods Administration

TGC Therapeutic Goods Committee

TGO Therapeutic Goods Order

TTHWP Trans-Tasman Harmonisation Working Party

TTMRA Trans-Tasman Mutual Recognition Agreement

WHO World Health Organization

WP Working Party

WS Warning statement



Delegatesrsquo reasons for final decisions July 2011 1

FINAL DECISIONS ON MATTERS NOT REFERRED TO ANADVISORY COMMITTEE

1 MEDICINES

11 SYNTHETIC CANNABINOIDS

BACKGROUND

Synthetic cannabinoids (or synthetic cannabinomimetics) comprise a number of groups of chemically unrelated structures all of which are functionally similar to the activeprinciple in cannabis delta-9-tetrahydrocannabinol (THC)

Effects of synthetic cannabinoids are due to their agonist activity at the cannabinoidreceptors CB1 and CB2 CB1 is the receptor thought responsible for the euphoric and

psychoactive effects of cannabis CB2 is mainly found in the immune system and mayplay a role in pain control as well as mood and behaviour regulation

The binding affinities for the CB1 and CB2 receptors vary between the various syntheticcannabinoid substances For example JWH-018 binds to both receptors with a higheraffinity than THC and this is the likely reason for the assumption that this substance maybe 4-5 times more potent that cannabis However the binding affinity of a substance fora receptor does not necessarily indicate strength of psychoactive effect

Many of these synthetic cannabinoids were synthetised with the aim of using them as alaboratory tool to identify marijuana receptors and to determine the mechanism of actionof cannabis Others have been developed as part of efforts to find new drugs for nausea

glaucoma and appetite suppression but few appear to have moved past the preliminarytesting stage Synthetic cannabinoids may also be used in pharmacological studiesinvolving structure-activity relationships receptor binding studies and mechanisms of action studies

Some synthetic cannabinoids have been used for medicinal purposes

middot Rimonabant (currently in Schedule 4) A selective CB1 receptor antagonist whichwas used to treat obesity for some time but was withdrawn from the market due tosevere side effects

middot Nabilone (currently in Schedule 8) A synthetic cannabinoid used for treatment of anorexia and for its antiemetic effects (eg in cancer patients under chemotherapy)

its chemical structure is closely related to THCmiddot Dronabinol (currently in Schedule 8 for therapeutic use) Synthetically produced pure

THC applied in multiple sclerosis and pain patients

Recreational use

There were reports of a number of synthetic cannabinoids being used recreationally as alsquolegalrsquo substitute for cannabis These substances appeared to be added to (sprayed onto)mixtures of dried herbs which were then smoked in order to obtain an effect similar to




cannabis Use as a herbal tea was uncommon due to the lipophilic compoundsrsquo lowsolubility in water

Due to the lack of quantitative information about the amount of synthetic cannabinoidsincorporated into the herbal smoking blends caution should be exercised when drawingany conclusions about comparison of the strength of these products with cannabis

Recreational use of these products was reported in Europe the US Asia New Zealandand Australia Commonly used names for these products included lsquoKronicrsquo and lsquoSpicersquoIn Europe lsquoSpicersquo was commonly used as a proprietary eponym to describe the entireclass of products In Australia and New Zealand product names included lsquoKarmarsquolsquoVoodoorsquo and lsquoKaosrsquo and in the US a commonly used brand was lsquoK2rsquo

At this time these products were available over the Internet and through specialty storesWebsites where these herbal smoking blends could be purchased commonly promotedthem as lsquolegal highsrsquo The products were also sold as lsquoherbal incensersquo and in somecountries as lsquoplant foodsrsquo

Australian jurisdictional activities

On 17 June 2011 Western Australia (WA) implemented a ban via state-specificlegislation on the seven synthetic cannabinoids as listed in the WA scheduling requestbelow However several days after the release of the intent to ban these substances analternative synthetic cannabinoid formulation was being marketed claiming to circumventthese controls

On 17 June 2011 South Australia (SA) also implemented a ban via state-specificlegislation on 17 synthetic cannabinoids (including the seven prohibited by WA)

Certain other jurisdictions were also investigating alternate state-specific approaches such

as capturing synthetic cannabinoids lsquointendedrsquo to have a substantially similarpharmacological effect to cannabis This outcome-based approach is also possible underthe scheduling system where substances may be scheduled based on effect rather thanchemical structure (eg the current entry for antibiotic substances captures substanceswhich vary widely in structure and mode of action) Inclusion of a clause ldquoexcept whereseparately specifiedrdquo in the Schedule entry would then allow for appropriate schedulingof individual substances which may have profiles different from the general class

SCHEDULING STATUS

Apart from rimonabant nabilone and dronabinol (as described above) there appear to beno other specific entries for synthetic cannabinoids A limited number of cannabinoids

may be captured as derivatives in accordance with Part 1 (2) of the Standard for theUniform Scheduling of Medicines and Poisons (SUSMP) (eg HU-210 is captured as aderivative of nabilone)

Almost all of the synthetic cannabinoids under consideration (except somedibenzopyrans) have chemical structures unrelated to currently scheduled cannabinoidsand were therefore not likely to be captured as derivatives by existing entries




PART 1 - Interpretation

(2) Unless the contrary intention appears a reference to a substance in aschedule or an appendix to this Standard includes

(a) that substance prepared from natural sources or artificiallyand

(b) where the substance is a plant (other than a plant included inSchedule 8 or 9) that plant or any part of that plant whenpacked or prepared for therapeutic use and

(c) every salt active principle or derivative of the substanceincluding esters and ethers and every salt of such an activeprinciple or derivative and

(d) every alkaloid of the substance and every salt of such analkaloid and

(e) every stereoisomer of the substance and every salt of such astereoisomer and

(f) every recombinant form of the substance and

(g) a preparation or admixture containing any proportion of thesubstance

A substance is not classed as a derivative on the basis of a single prescriptive set of

criteria Classification of a substance as a derivative of a Scheduled poison relies on abalanced consideration of factors to decide if a substance has a similar nature (egstructurally pharmacologically toxicologically) to a Scheduled poison or is readilyconverted (either physically or chemically) to a Scheduled poison

SUBMISSIONS

WA Request

The WA State Drugs and Poisons Unit submitted a request for

middot A delegate-only final decision to include in Schedule 9 seven of the most commonlydetected individual synthetic cannabinoids with demonstrated harmful effects or

potential for significant harmful effects and

middot A referral to the Advisory Committee on Medicines Scheduling (ACMS) for adviceon the inclusion in Schedule 9 of broader synthetic cannabinoid groups

Scheduling of individual synthetic cannabinoids

The request stated that rapid scheduling of the individual actives could be justified due tothe potential for significant public health risk noting that the substances underconsideration were new chemical entities not previously scheduled




The request recommended that the substances listed in the following table be included inSchedule 9 on the basis that they are used for the purpose of obtaining a psychoactiveeffect may be dependence producing have no legitimate therapeutic uses and havedocumented harmful effects which may be significant in some individuals

Common name CAS Chemical name(s) inMartindale

International Union of Pureand Applied Chemistry(IUPAC) systematic name

JWH ndash 018 209414-07-3 1-Naphthalenyl(1-pentyl-1H-indol-3-yl)methanone

1-Pentyl-3-(1-naphthoyl)indole

JWH ndash 073 208987-48-8 1-Naphthalenyl(1-butyl-1H-indol-3-yl)methanone

JWH-018 butyl homologue

Naphthalen-1-yl-(1-butylindol-3-yl)methanone

JWH ndash 122 619294-47-2 nil 1-Pentyl-3-(4-methyl-1-naphthoyl)indole

JWH ndash 200 103610-04-4 nil (1-(2-morpholin-4-ylethyl)indol-3-yl)-naphthalen-1-ylmethanone

JWH ndash 250 864445-43-2 nil 2-(2-methoxyphenyl)-1-(1-pentylindol-3-yl)ethanone

CP 47497 70434-82-1 (1RS3SR)-3-[2-hydroxy-4-(2-methyloctan-2-yl)phenyl]cyclohexan-1-ol

2-[(1R3S)-3-hydroxycyclohexyl]- 5-(2-methyloctan-2-yl)phenol

Cannabicyclohexanol

(CP 47497 C8homologue)

70434-92-3 (1RS3SR)-3-[2-hydroxy-4-(2-methylnonan-2-yl)phenyl]cyclcohexan-1-ol

2-[(1R3S)-3-hydroxycyclohexyl]-5-(2-methylnonan-2-yl)phenol

XXXXX recommended use of the IUPAC systematic name to identify the variouschemicals The request also suggested that for clarity it may be necessary to include boththe chemical name and the more widely used abbreviated names (ie JWH-018 andCP 47497) in the schedule entries and the SUSMP Index

These substances have either been included in Schedule I of the US Federal Controlled

Substances Act (also controlled by a number of European countries) or known to havebeen detected in products for sale in Australia Some European countries have alsoscheduled CP 47497 and its C6 C8 and C9 homologues The request suggested thatthese particular homologues may also need scheduling to ensure appropriate restrictions

The request also suggested an alternative outcome-based approach similar to theNorwegian drug control legislation where an entry could be included in Schedule 9 forldquosynthetic agonists of cannabinoid receptors or synthetic cannabinomimeticsrdquo However




noted that there were issues associated with this approach similar to those of schedulingthe group entries

Scheduling of groups of synthetic cannabinoids

The groups below have either been reported in smoking mixtures (both overseas and inAustralia) or have been controlled in other countries These groups were also requestedfor scheduling consideration and inclusion in Schedule 9

middot Dibenzopyrans (lsquoclassicalrsquo cannabinoids) ndash eg HU-210 and HU-211 THC(It was noted that due to their chemical structure HU-210 and HU-211 could becaptured under the derivatives clause by the Schedule 8 nabilone entry)

middot Cyclohexylphenols (lsquonon-classicalrsquo cannabinoids) ndash eg CP 47497 Analog VII orcannabicyclohexanol

middot Naphthoylindoles ndash eg JWH-015 JWH-018 JWH-073 JWH-122 JWH-200 JWH-210 JWH-398 WIN-55212

middot Naphthylmethylindoles

middot Naphthoylpyrroles

middot Naphthylmethylindenes

middot Phenylacetylindoles ndash eg JWH-250 JWH-251

Clarification was requested whether the dibenzopyrans class would be captured aslsquoderivativesrsquo by the existing Schedule 9 tetrahydrocannabinols entry If it was decidedthat these substances were captured as derivatives a cross reference in the SUSMP Indexwas suggested to clarify the scheduling status However if was determined that the

tetrahydrocannabinols entry did not capture this class of substances then requested toalso include dibenzopyrans in Schedule 9

The request raised concerns that if only certain substances within each chemical groupwere scheduled those manufacturing these products would move to a different compoundthat is similarly pharmacologically active There is evidence that this has occurred inother countries within weeks of the prohibition of certain synthetic cannabinoids

It was suggested that the inclusion of group entries would circumvent this issueHowever it was noted that in the UK where this approach was used in December 2009to control groups of chemical compounds through theMisuse of Drugs Act 1971 othersynthetic cannabinoids have since appeared in products within the UK which were not

captured by these groupsAlthough there was a lack of evidence of industrial use for the compounds captured bythe UKrsquos broad scheduling approach the submission noted that if the above group entrieswere included in Schedule 9 there may be potential for impact on future drugdevelopment by pharmaceutical manufacturers

According to the SUSMP listing a substance or class of substances in Schedule 9 wouldallow access to those substances for medical or scientific research or for analytical




teaching or training purposes with approval of Commonwealth andor State or TerritoryHealth Authorities However it is within the jurisdictionsrsquo means not to grant approvalto these substances for access in clinical trials

The request noted that referral of a proposal to schedule these group entries to the ACMSwould be subject to public consultation which would help inform of any unintendedconsequences of the proposed scheduling

The request also specifically addressed a number of matters under section 52E of the Therapeutic Goods Act 1989(the Act) as summarised below

Risks and benefits (including toxicity)

middot Some users of herbal smoking blends containing synthetic cannabinoids havereported similar effects to cannabis such as relaxation and sedation Commonlyreported effects included paranoia anxiety racing thoughts and irritability Othereffects included hallucinations tremors seizures drowsiness slurred speech dilated

pupils elevated blood pressure vomiting and chest pain There have also beenreports of the use of synthetic cannabinoids precipitating the redevelopment of psychosis in patients with a history of mental illness (similar rates to those associatedwith cannabis use)

middot The smoking of any substance is likely to have an adverse effect on health and likethe smoking of tobacco and cannabis herbal smoking blends may put users at risk of developing pulmonary conditions such as chronic bronchitis and lung cancerAnother potential concern with these substances was the possibility of serotoninsyndrome The indole moiety in certain compounds in the JWH series results in asimilar structure to serotonin and may increase serotonin receptor activation (Thedelegate noted that if the JWH substances under consideration were scheduled the

overall structure of these substances was sufficiently different so as not toinadvertently capture serotonin as a derivative)

middot Claims have also been made in the media that herbal smoking mixtures allegedlycontaining synthetic cannabinoids have been responsible for at least three deaths inthe US However one of these deaths was subsequently shown to be the result of alsquomixed drug intoxicationrsquo and there was no coronial information available on the roleof these products in the other two deaths

middot There was no scientific literature describing the long-term effects of either thesynthetic cannabinoids themselves or the effects of smoking the herbal blends Therelatively short period of use within populations (probably since 2008) was

insufficient to examine longer-term effects such as onset of mental illness andassociations with cancer

middot There was a lack of peer reviewed literature of systematically conducted trials of either the toxicology or potential beneficial effects of these substances in man Therewas limited animal toxicology data available for some synthetic cannabinoids Therewas also little information about the potential health effects of the herbs used ascarriers for the synthetic cannabinoids




middot Determining prevalence of use was hampered by difficulties in detecting both theparent compound and metabolites in urine samples and prior to 2008 there was nomechanism for recording synthetic cannabinoid related admissions to health servicesIn Australia it was likely that hospital admissions would be recorded as relating to

lsquocannabis derivativesrsquo and therefore at this time it was not possible to ascertain theproportion of admissions due to these synthetic substances

Purpose and extent of use

middot None of the seven substances requested by WA have any current legitimate humantherapeutic use Although there were anecdotal claims of antidepressant antinauseaand pain relieving effects the initial choice to use synthetic cannabinoids was almostalways for the purpose of obtaining a psychoactive effect

middot There were claims that synthetic cannabinoids have been used as an alternative tosmoking cannabis and hence should remain lsquolegalrsquo as users were therefore able toremove themselves from the illicit market

middot It was also suggested that use of these products was more popular in novice drugusers hoping to get a lsquohighrsquo whilst avoiding breaking the law It could be suggestedthat this increases risk of use by younger persons

middot In WA consumers have indicated that they chose to use these types of preparations asan alternative to cannabis because the substances in these herbal smoking mixtureswere not detected in drug screening tests used by their employers Recent mediareports from New Zealand (NZ) also indicated that employers are concerned aboutuse of lsquoherbal highsrsquo in high risk industries such as transport civil engineeringaviation and mining

Dosage formulation labelling etcmiddot Herbal smoking products available at this time did not indicate which synthetic

cannabinoids they contained or in what quantities Packages generally contained 1 gor 3 g of crushed dried plant matter

middot Testing has shown that a product sold under the same brand at different times maycontain different synthetic cannabinoids in varying quantities (between 23 mgg and229 mgg of CP 47497-C8 JWH-018 or JWH-073)

middot Some products were labelled to suggest they should not be used by those under18 years of age Other products were labelled as lsquonot for human consumptionrsquo(suggesting that they were intended to be burned as room incense rather than being

smoked)

Potential for abuse misuse

middot There were reports of patients meeting the standard criteria for both withdrawal andaddiction in relation to use of certain synthetic cannabinoid herbal blends withevidence of tolerance and withdrawal symptoms Specific reports have alsosuggested that JWH-018 was associated with drug tolerance most likely due to




receptor down-regulation This was thought to generally increase the likelihood of dependence on that drug where the drug has psychoactive effects

middot At least three synthetic cannabinoids were detected in herbal blends purchased in WAretail outlets JWH-073 JWH-122 and JWH-250 Products claiming to bemanufactured in NZ and sold in NZ and Australia have also been shown to contain JWH-018

United Nations Office on Drugs and Crime (UNODC)

The UNODC released a report on synthetic cannabinoids in herbal products focusing onthe substancesrsquo pharmacological activity potential toxicity and recommendationsregarding their legal handling The report made the following points not previouslymentioned

middot Since 2004 herbal mixtures containing synthetic cannabinoids have been available inseveral European countries Initially these products were not popular and were used

by only a small group of experimental users However numerous reports on theseproducts surfaced in German newspapers and television in 2008 proclaiming their useas lsquolegalrsquo cannabis substitutes leading to dramatic increases in popularity

middot While these products were initially found to be popular among users of different agesand socioeconomic status a recent survey suggested that the use of these productshad dropped significantly However it was still increasingly popular among userswho have to undergo regular urine drug screenings as current screening methods didnot detect synthetic cannabinoids

middot In addition to the seven groups of synthetic cannabinoids requested by WA theUNODC also provided details on the following synthetic cannabinoid groups

- Benzoylindoles ndash eg pravadoline AM-694 RSC-4

- Eicosanoids ndash endocannabinoids (substances produced from within the body thatactivated cannabinoid receptors) such as anandamide and their syntheticanalogues eg methanandamide and

- Diarylpyrazoles ndash selective CB1 antagonists eg rimonabant (listed inSchedule 4)

middot Noted that synthetic cannabinoids commonly used in pharmacological studiesincluded CP-55940 (a cyclohexylphenol) WIN-55212-2 (a naphthoylindole) andanandamide (an eicosanoid)

middot Noted the adverse effects associated with use of synthetic cannabinoids specificallythe increasing numbers of hospitalisations with severe intoxications following use of products claimed to contain JWH-122

middot Stated that there was no valid data on the toxicity of these compounds so far howeverit could be speculated that some of the metabolites particularly those carrying anaphthyl moiety may have carcinogenic potential




middot Stated that although cannabis has a comparatively low acute toxicity at least some of the synthetic compounds under consideration could cause severe or life-threateningintoxications when overdosed particularly those which act as full agonists at the CB1receptor (HU-210 CP-55940 or WIN-55212-2)

middot Noted evidence which suggested that a number of synthetic cannabinoids may have ahigher addictive potential compared to cannabis due to quicker development of tolerance

middot Stated that the herbal blend phenomenon did not seem to disappear in countries whichprohibited either single actives or groupings of synthetic cannabinoids although thenumber of users may have been reduced due to lower availability and lesser mediapresence Noted that there remained a variety of these products available on theInternet with new synthetic cannabinoids continuously appearing

middot Noted that the use of a generic definition for controlling synthetic cannabinoidswould still bear the risk of not covering all possible derivatives and may possiblyhamper synthetic cannabinoid research

International considerations

Initial reports of use appeared in Europe around 2008 with increases leading to the UNInternational Narcotics Control Board (INCB) expressing concern with the level of useAlthough none of the synthetic cannabinoids are listed in either theUnited Nations SingleConvention on Narcotic Drugs 1961or theUnited Nations Convention on PsychotropicSubstances 1971 the INCB considers the availability of herbal mixtures containing thesesubstances to be a matter of concern The INCB recently issued a statement in whichthey welcomed the timely efforts of governments to prevent the trafficking in and abuse

of synthetic cannabinoids and recommended the continued monitoring of the situationand the adoption of preventative measures as necessary

A number of jurisdictions with similar regulatory frameworks to Australia haveimplemented controls on access to these substances including the UK (December 2009)and the US (March 2011)

Europe

In the UK Schedule 1 of the Misuse of Drugs Regulations 2001 results in the moststringent controls under those Regulations where substances are not authorised formedical use and can only be supplied possessed or administered in exceptionalcircumstances under a special Home Office licence usually only for research purposes

Class B drugs are subject to both possession and dealing offences (resulting in up to5 years imprisonment and up to 14 years imprisonment respectively) The followingsubstances were added to Schedule 1 and classified as lsquoClass Brsquo

middot 3-(1-naphthoyl)indole or 1H-indol-3-yl-(1-naphthyl)methane

middot 3-(1-naphthoyl)pyrrole

middot 1-(1-naphthylmethyl)indene




middot 3-phenylacetylindole and

middot 2-(3-hydroxycyclohexyl)phenol

In mainland Europe several countries have enacted controls on a number of different

synthetic cannabinoids varying from prohibition of distribution to prohibition of anyactivities (sometimes with provision for access by authorisation for some research typeactivities) Certain countries have also prohibited use of any substance with cannabinoidactivity

USA

In the US Schedule I is the most restrictive Schedule of theControlled Substances Act (CSA) where possession and supply (including import and export) of a substance isillegal except as authorised by law From 1 March 2011 the US Drug EnforcementAdministration (DEA) added five synthetic cannabinoids (JWH-018 JWH-073 JWH-200 CP-47497 and cannabicyclohexanol) to Schedule I to lsquoavoid an imminent hazard to

the public safetyrsquo A summary of the actions undertaken by the DEA is provided belowmiddot This scheduling will remain in place for at least 12 months (with the option of a 6

month extension) while the US Department of Health and Human Services furtherinvestigates whether these chemicals should be permanently controlled

middot The DEA considered a number of factors prior to making a decision including thehistory and current pattern of abuse the scope duration and significance of abuseand what if any risk there is to the public health including actual abuse diversionfrom legitimate channels and clandestine importation manufacture or distribution

middot Three reasons were given for the US DEA action

-

Although the substances are not intended for human consumption there has beena rapid and significant increase in abuse in the US

- Law enforcement agencies have seized lsquosynthetic cannabinoidsrsquo with controlledsubstances and based on self-reports to law enforcement and health careprofessionals synthetic cannabinoids are abused for their psychoactive propertiesand

- Numerous state and local public health department and poisons control centreshave issued health warnings describing the adverse health effects associated withsynthetic cannabinoids

middot Asserted that these five substances were developed and evaluated as research tools

were not intended for human consumption and no other known legitimate uses havebeen identified

middot Noted that smoking these synthetic cannabinoids for the purpose of achievingintoxication and experiencing the psychoactive effects has been identified as a reasonfor emergency room visits and calls to poison control centres




New Zealand (NZ)

In November 2010 the NZ Expert Advisory Committee on Drugs considered anassessment of the synthetic cannabinoids JWH-018 and JWH-073 In summary theassessment made a number of points specific to NZ not previously mentioned

middot Noted that in March 2009 the 11-dimethyloctyl homologue of CP 47497 wasbanned following determination that it was structurally related to THC

middot Following this ban other synthetic cannabinoids appeared on the market including JWH-018 and JWH-073 Noted that this trend was mirrored in other jurisdictionswhich had also prohibited single actives

middot Noted the lack of available evidence of prevalence of synthetic cannabinoidscurrently available in NZ however identified at least 80 synthetic cannabinomimeticsubstances derived from naphthoylindoles phenylacetylindoles benzoylindolesnaphthoylpyrroles cyclohexylphenols and classical cannabinoids Noted that due to

their structural similarity some classical cannabinoids could be captured by therestrictions on THC

middot Noted a submission recommending Class C (Controlled Drug) restrictions on thefollowing substances

- JWH-018 (a naphtholindole) due to issues with toxicity and abuse potential Thiscompound had proved unusually problematic and had a particular tendency tocause anxiety and serious adverse reactions even when diluted in herbal smokingblends

- HU-210 (a classical cannabinoid) due to significant potency severe side effectsand very long duration of action

- AM-694 (a benzoylindole) due to toxicity concerns relating to its chemicalstructure

middot Noted that the increase in media attention on synthetic cannabinoids may have led toan increase in use Also noted an increase in marketing of these products to youngpeople

middot Noted the significant rates of use of these products in secure inpatient mental healthservices Noted anecdotal evidence that these high use patterns were mostly due to alack of proper detection techniques

middot Stated that there was no peer reviewed literature on the toxicological effects of the

JWH compounds however noted an anonymous study available on the internetclaiming data on fluorescent cytochrome P450 inhibition cytotoxicity genotoxicityQT interval prolongation rat pharmacokinetics and repeat rat toxicity for JWH-018

middot Noted a submission which stated that naphthoylindoles JWH-018 and JWH-073 mayhave a greater tendency to produce anxiety and paranoia than THC

middot Stated that the NZ Ministry of Health was not aware of any research into the effect ondriving performance of the substances JWH-018 or JWH-073 However given the




sedating and hallucinatory effects expected of substances which act as a CB1 agonistit was likely that a person could become significantly impaired following the use of these substances

middot Noted that apart from anecdotal reports there was no officially recognised therapeuticuse of JWH substances Stated that as certain therapeutic aspects of cannabis may bereproduced more strongly by synthetic cannabinomimetic drugs with a higher affinityfor the CB1 and CB2 receptor than cannabis these substances may have efficacy intreating certain conditions Noted however no pharmaceutical preparationscontaining the JWH compounds have been brought to market

middot Noted a submission which stated that the UK approach to restricting class entriesmissed a number of substances such as AM-694 (1-(5-fluoropentyl)-3-(2-iodobenzoyl)indole) which has since been brought to the market in these jurisdictions

The minutes of the NZ EACD meeting provided the following additional pointssummarised below

middot The EACD agreed that it was not only the delivery of these substances (via smoking)that may be harmful but the substances themselves It was noted that there stillexisted a lack of robust scientific data on these substances and regulation of thesesubstances as restricted would ensure that accessibility controls would be in place tomitigate some risks while allowing for the substances to be monitored more closely

middot EACD members discussed the potential appeal to vulnerable populations and it wasacknowledged that marketing for these products would continue to grow Also notedthe possibility that such regulation could increase aggressive marketing techniques astheir restricted status might inadvertently convey a sense of government endorsement

middot A common concern was that other synthetic cannabinomimetic substances mayemerge in place of JWH-018 and JWH-073 once these were restricted Alternativegrouping entries such as ldquonaphthoylindole derivativesrdquo were considered as these werecurrently the most widely available and cheapest on the chemical market andtherefore the most likely to be incorporated into smoking products by the industry

middot It was concluded that the most effective measure would be to try to capture newemerging cannabinomimetic substances by recommending that ldquoall syntheticsubstances with cannabinomimetic effectsrdquo be included in theMisuse of Drugs Act1975as restricted substances In the event that this approach was not legally possibleunder NZ legislation decided to include the naphthoylindole derivatives individually

as restricted substances to capture the most potent easily available and therefore mostlikely substances to be utilised by this industry

middot In NZ classifying a substance as restricted allows access to that substance subject tostipulated conditions and restrictions




Unsolicited stakeholder input

Although an invitation for submissions was not published several unsolicited commentswere received likely in response to the jurisdictionsrsquo implementation of state-specificcontrols and resulting media attention The delegate was under no legislative obligationto consider these comments

Intergovernmental Committee on Drugs (IGCD)

The Chair of the IGCD supported the WA request for inclusion of synthetic cannabinoidsin Schedule 9 and requested an accelerated consideration A number of comments werealso provided as summarised below

middot At the May 2011 IGCD meeting members noted the emergence of new and existingsynthetic analogue drugs (analogues) that mimic the effects of illegal drugsparticularly substances in herbal blends which mimic the effects of cannabis

middot Noted the reported wide use of these substances particularly in the mining industry

Raised concerns over health and safety particularly for employees operatingmachinery Also raised concerns about the risk to public health and safety from thecontinued sale of herbal blends with synthetic cannabinoids as the ingredients purityand pharmacological potency of such products were largely unknown

Department of Health Victoria

Victoria Health supported the urgent consideration and restriction of syntheticcannabinoids and submitted for consideration the following points not previouslymentioned

middot In May 2011 there was limited data on the extent of the use of these herbal blends in

Victoria however there were anecdotal reports of open promotion and sale through avariety of stores and the internet

middot Regular Alcohol amp Other Drug (AOD) monitoring reports have not at this timedetected harms from any analogue drug or significant levels of use of this category of drug amongst AOD service users

middot Supported regulation of analogues to

- in the short term allow the temporary prohibition of new analogues until riskscould be properly assessed and longer-term regulation put in place and

- in the longer term be flexible enough to ensure that new and harmfulpsychoactive substances would be captured by regulations without continual needfor updating

middot Requested that options for addressing issues relevant to analogues be exploredincluding in the context of the Customs (Prohibited Imports) Regulations

middot Is currently awaiting advice from the IGCD on mechanisms to identify emergingpsychoactive substances as soon as they appear on Australian markets assess theharms develop regulatory and administrative responses and disseminate timelywarning information to agencies and the public




XXXXX

XXXXX submitted a request to align with the NZ decision to restrict syntheticcannabinoids such as JWH-018 and JWH-073 instead of banning The request assertedthat a number of states had existing restrictions on the supply of non-tobacco smokingsubstances

XXXXX

XXXXX objected to prohibiting synthetic cannabinoids specifically in relation to JHW-018 and suggested an alternate regulatory approach similar to NZrsquos classificationSuggested inclusion in Schedule 6 as the closest to the NZ classification or alternativelythe creation of a sub-class of Schedule 7 reserved for lsquosocial inebriantsrsquo Suggestedmandatory training for licensed vendors and their staff

The majority of the inputrsquos comment related to the potential revenue of regulatingsynthetic cannabinoids and where this revenue would be diverted should these substances

be prohibited The input also asserted that in concentrations of less than 10 mg per gram of carriersubstance JWH-018 was relatively safe and only mildly inebriating and did not induceparanoia or anxiety Asserted that the negative reactions reported in Australia to datewere due to use of higher concentrations of the product

DELEGATErsquoS DISCUSSION

In accordance with section 52E(4) of the Therapeutic Goods Act 1989(the Act) thedelegate sought verbal advice on this matter from representatives of Australian jurisdictions with expertise in drugs and poisons regulation

The delegate agreed that for this consideration the relevant matters under section 52E(1)of the Act included (a) risks and benefits of use (b) purpose and extent of use and (e) thepotential for abuse of a substance

The delegate agreed that this matter required a two-phased approach

middot The consideration of restrictions to a number of individual synthetic cannabinoids toaddress the immediate risks to public health and

middot The development of a longer-term solution to appropriately capture relatedsubstances

Individual substances

The delegate noted the factors listed in the Scheduling Policy Framework for inclusion of substances in Schedule 9 The delegate noted that there was currently no evidence of established therapeutic value for the seven synthetic cannabinoids identified in the WArequest (JWH-018 JWH-073 JWH-122 JWH-200 JWH-250 CP47497 andcannabicyclohexanol) The delegate also noted the risks associated with thesesubstances including their potential for dependency abuse and misuse




The delegate additionally noted current reports of abuse and misuse of AM-694 (abenzoylindole) The delegate agreed that although this substance was not identified inthe WA request its profile also aligned with the factors for inclusion in Schedule 9 Thedelegate further noted that this substance was already specifically prohibited in SA via

state-specific legislation along with a number of other benzoylindoles

The delegate noted input from stakeholders suggesting alternative approaches toinclusion in Schedule 9 including alignment with NZ restrictions or the creation of aprohibitive category for specific Australian sub-populations The delegate decided thatsuch an approach was not appropriate for Australia and noted that such controls were alsonot possible under the current Australian scheduling arrangements

The delegate also noted claims of alleged benefits of revenue from use of syntheticcannabinoids The delegate clarified that scheduling decisions are made to protect publichealth and Schedule 9 controls for synthetic cannabinoids would assist in reducing harmassociated with these substances

On balance the delegate agreed that the dangers of use of these eight syntheticcannabinoids were such as to warrant limiting use to strictly controlled medical andscientific research The delegate agreed to specifically list these substances inSchedule 9 using their IUPAC names to ensure clarity and assist enforcement Thecommon names of these substances would also be cross-referenced to these entries inboth Schedule 9 and the SUSMP Index For clarity the delegate also agreed that a cross-reference in the SUSMP Index from the C6 and C9 homologues of CP 47497 to 2-[(1R3S)-3-hydroxycyclohexyl]-5-(2-methylnonan-2-yl)phenol (iecannabicyclohexanol) would be appropriate

The delegate noted that the decision to include these eight substances in Schedule 9 was a

final decision initiated by the delegate (by request) and as such was not subject to furthersubmissions The delegate also noted that under the SUSMP derivatives clause theSchedule 9 entries for the eight individual substances would also capture many similarsubstances

Implementation date

The delegate noted that due to the potential of the use of these substances to cause harm ashorter implementation period would be required than those reserved for routinescheduling decisions The delegate agreed that an implementation date of 8 July 2011would be appropriate for this decision

Synthetic cannabinoid classes

The delegate noted the request for the scheduling of classes of cannabinoids to limitpotential future abuse of substances replacing those which have been prohibited

Although some cannabinoids would be captured as derivatives of the eight substancesdetailed above this clause may not extend to all substances within those classes Thedelegate also noted the risk of users potentially moving onto substances within othersynthetic cannabinoid classes not currently captured by these restrictions The delegate




noted that listing all the known classes of synthetic cannabinoids in Schedule 9 as groupentries could address these two potential issues

The delegate also noted that new classes of synthetic cannabinoids could be created formisuse purposes The delegate noted other jurisdictionsrsquo approaches to address this issueby inclusion of an outcome-based class entry either for all synthetic agonists of cannabinoid receptors or substances intended to have a substantially similarpharmacological effect to cannabis

The delegate noted that according to the SUSMP class entries do not capture substanceswhich are individually listed (for example the existing Schedule 9 class entry fortetrahydrocannabinols does not capture nabiximols as it is separately listed) Howeverother substances within those classes which are not specifically scheduled would then becaptured

The delegate agreed that due to the complexity of any group entry approach and thepotential for inadvertent impact on substances not currently scheduled this matter would

benefit from advice from the ACMS The delegate noted that referral of this matter to theACMS also allows for public consultation with an invitation for public submissions onthe delegatersquos proposal to be published on the TGArsquos scheduling website on10 August 2011

DELEGATErsquoS FINAL DECISION

The delegate decided to include in Schedule 9 the following synthetic cannabinoidstogether with reference to their common names noting that many analogues of thesesubstances would also be captured as derivatives

middot (1-(5-fluoropentyl)-3-(2-iodobenzoyl)indole) (common name AM-694)

middot 2-(2-methoxyphenyl)-1-(1-pentylindol-3-yl)ethanone (common name JWH ndash 250)

middot (1-(2-morpholin-4-ylethyl)indol-3-yl)-naphthalen-1-ylmethanone (common name JWH ndash 200)

middot Naphthalen-1-yl-(1-butylindol-3-yl)methanone (common name JWH ndash 073)

middot 1-Pentyl-3-(4-methyl-1-naphthoyl)indole (common name JWH ndash 122)

middot 1-Pentyl-3-(1-naphthoyl)indole (common name JWH- 018)

middot 2-[(1R3S)-3-hydroxycyclohexyl]-5-(2-methylnonan-2-yl)phenol (common nameCannabicyclohexanol or CP 47497 C8 homologue) and

middot 2-[(1R3S)-3-hydroxycyclohexyl]- 5-(2-methyloctan-2-yl)phenol (common nameCP 47497)

For clarity the delegate also decided that in addition to the usual SUSMP Index cross-referencing of the common names to the Schedule 9 listing to also include a cross-reference in the Index from the C6 and C9 homologues of CP 47497 to 2-[(1R3S)-3-hydroxycyclohexyl]-5-(2-methylnonan-2-yl)phenol (cannabicyclohexanol)




The delegate decided on an implementation date of 8 July 2011

Schedule 9 ndash New Entries

(1-(5-FLUOROPENTYL)-3-(2-IODOBENZOYL)INDOLE) (AM-694)

2-(2-METHOXYPHENYL)-1-(1-PENTYLINDOL-3-YL)ETHANONE(JWH ndash 250)

(1-(2-MORPHOLIN-4-YLETHYL)INDOL-3-YL)-NAPHTHALEN-1- YLMETHANONE (JWH ndash 200)

NAPHTHALEN-1-YL-(1-BUTYLINDOL-3-YL)METHANONE (JWH ndash 073)

1-PENTYL-3-(4-METHYL-1-NAPHTHOYL)INDOLE (JWH ndash 122)

1-PENTYL-3-(1-NAPHTHOYL)INDOLE (JWH - 018)

2-[(1R3S)-3-HYDROXY CYCLOHEXYL]- 5-(2-METHYLOCTAN-2-YL)PHENOL(CP 47497)

2-[(1R3S)-3-HYDROXY CYCLOHEXYL]-5-(2-METHYLNONAN-2-YL)PHENOL(Cannabicyclohexanol or CP 47497 C8 homologue)



Delegatesrsquo reasons for final decisions July 2011 i

TABLE OF CONTENTS

GL OSSARY II FINAL DECISIONS ON MATTERS NOT REFERRED TO AN ADVISORY COMMITTEE 1 1 MEDICINES 1

11 S YNTHETIC CANNABINOIDS 1




GLOSSARY

ABBREVIATION NAME





































































OOS Out of Session


















Poisons [SUSMP])













WP Working Party






1 MEDICINES


BACKGROUND












Recreational use














SCHEDULING STATUS


















SUBMISSIONS

WA Request























Cannabicyclohexanol
























































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date








































GLOSSARY

ABBREVIATION NAME





































































OOS Out of Session


















Poisons [SUSMP])













WP Working Party






1 MEDICINES


BACKGROUND












Recreational use














SCHEDULING STATUS


















SUBMISSIONS

WA Request























Cannabicyclohexanol
























































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date























































































OOS Out of Session


















Poisons [SUSMP])













WP Working Party






1 MEDICINES


BACKGROUND












Recreational use














SCHEDULING STATUS


















SUBMISSIONS

WA Request























Cannabicyclohexanol
























































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date































































OOS Out of Session


















Poisons [SUSMP])













WP Working Party






1 MEDICINES


BACKGROUND












Recreational use














SCHEDULING STATUS


















SUBMISSIONS

WA Request























Cannabicyclohexanol
























































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date








































OOS Out of Session


















Poisons [SUSMP])













WP Working Party






1 MEDICINES


BACKGROUND












Recreational use














SCHEDULING STATUS


















SUBMISSIONS

WA Request























Cannabicyclohexanol
























































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date














































WP Working Party






1 MEDICINES


BACKGROUND












Recreational use














SCHEDULING STATUS


















SUBMISSIONS

WA Request























Cannabicyclohexanol
























































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date









































1 MEDICINES


BACKGROUND












Recreational use














SCHEDULING STATUS


















SUBMISSIONS

WA Request























Cannabicyclohexanol
























































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date

















































SCHEDULING STATUS


















SUBMISSIONS

WA Request























Cannabicyclohexanol
























































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date



















































SUBMISSIONS

WA Request























Cannabicyclohexanol
























































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date





















































Cannabicyclohexanol
























































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date





















































































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date


































































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date



















































smoked)































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date

































































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date
















































Europe













USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date












































USA






-










New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date








































New Zealand (NZ)




















































XXXXX


XXXXX






















Implementation date









































































XXXXX


XXXXX






















Implementation date




























































XXXXX


XXXXX






















Implementation date








































XXXXX


XXXXX






















Implementation date















































Implementation date


















































































Documents

Scheduling Decisions 1107 Final